The Utility of Performing the Initial Lumbar Puncture on Day 8 in Remission Induction Therapy for Childhood Acute Lymphoblastic Leukemia: TCCSG L99-15 Study
ABSTRACT Traumatic lumbar puncture with leukemic blasts (TLP+), which has been reported to occur 5-10%, in the previous studies, adversely affects the outcome of children with acute lymphoblastic leukemia (ALL). Based on the results from our previous study, we deferred the initial lumbar puncture until day 8 in remission induction therapy in order to reduce the frequency of cases with TLP+.
The study was conducted as a prospective cohort study within the Tokyo Children's Cancer Study Group (TCCSG) L99-15 study. Between April 1999 and June 2003, 754 children with newly diagnosed ALL enrolled. The patients received the initial intrathecal chemotherapy after 7 days of prednisolone treatment. The incidence of central nervous system (CNS)-positive (the presence of leukemic blasts in cerebrospinal fluid or cranial nerve palsy) including TLP+ cases and cumulative incidence of CNS relapse were examined.
The incidence of CNS-positive and TLP+ was 2.9% (n = 22) and 0.8% (n = 6), respectively. These incidences were much lower than those in the representative study groups employing the initial IT on day 1. Of 22 patients with CNS-positive, only one patient relapsed in CNS, whereas 22 of the remaining CNS-negative 723 patients suffered from CNS relapse. Overall, event-free survival at 4 year was 78.2 ± 1.6%. Four-year cumulative incidence of any CNS relapse was 3.3 ± 0.7%, which improved from our previous study in spite of limiting the use of cranial irradiation.
Our strategy reduced the frequency of CNS-positive patients who required reinforcement of CNS-directed therapy without compromising overall outcome.
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ABSTRACT: There is no standard treatment for adolescents aged 15 years or older with acute lymphoblastic leukemia (ALL), although this age group has been reported as having a poorer prognosis compared to younger patients. We retrospectively analyzed the outcomes of three consecutive Tokyo Children's Cancer Study Group ALL trials (1995-2006) of 373 patients aged 10 years or older, with particular focus on adolescents aged 15-18 years (older-adolescents n = 41), compared to those aged 10-14 years (younger-adolescents n = 332). The probability of event-free survival at 8 years was 67.5 ± 7.4 % for the older-adolescents and 66.5 ± 2.6 % for the younger-adolescents (p = 0.95). Overall survival was 70.7 ± 7.1 % for the older-adolescents and 74.3 ± 2.4 % for the younger-adolescents (p = 0.48). The differences between groups in relapse incidence, non-relapse mortality, and death rate during induction were not statistically significant, although the older-adolescents trended towards a higher frequency of having stem-cell transplantation during the first remission. In conclusion, our treatment strategy, which consists of intensive induction and block-type consolidation, provided improved outcomes for patients aged 15-18 years, comparable to those for patients aged 10-14 years.International Journal of Hematology 06/2014; 100(2). DOI:10.1007/s12185-014-1622-y · 1.68 Impact Factor
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ABSTRACT: Relapse period is strongly associated with second relapse risk in relapsed acute lymphoblastic leukemia (ALL) in children. In this context, the treatment outcome of very late relapse should be better; however, data regarding very late relapse is limited. We retrospectively analyzed the outcomes of two consecutive Tokyo Children's Cancer Study Group (TCCSG) ALL trials (1995-2004) with a focus on late relapse, which was divided into two categories: late relapse (6-24 months from the end of therapy, n = 48) and very late relapse (>24 months from the end of therapy, n = 57). Forty-three patients (29 late relapse and 14 very late relapse) received allogeneic hematopoietic stem cell transplantation (HSCT) at second remission. The event-free survival (EFS) probabilities of late relapse and very late relapse were 54.5 ± 7.3 and 64.8 ± 6.8 % at 7 years, respectively (P = 0.36), and were not significantly different. However, the second relapse incidence of late relapse (34.7 ± 7.1 %) was higher than that of very late relapse (15.5 ± 5.1 %, P = 0.03). The second relapse risk was low for very late relapse ALL, which suggests that these patients should be treated without allogeneic HSCT.International Journal of Hematology 11/2014; 101(1). DOI:10.1007/s12185-014-1710-z · 1.68 Impact Factor
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ABSTRACT: To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts from peripheral blood (PB) for up to 10 days of multidrug induction, and CrRT was omitted in all patients. If PB blasts persisted on treatment day 10 (d10), the TIT was then performed. Of a total of 156 patients, 152 were eligible. Seventeen patients did not have PB blasts at diagnosis. Three fourths of the remaining patients achieved complete clearance of PB blasts by d10. Only hyperleukocytosis at diagnosis showed a significantly lower clearance rate. Six standard-risk patients were upgraded to high risk because of detectable PB blasts on d10. TLPs were encountered in four patients (2.6%), but none were contaminated with lymphoblasts. Neither CNS-2 (less than 5 WBCs/μ L with blasts in a nontraumatic sample) nor CNS-3 (≥ 5 WBCs/μ L with blasts in a nontraumatic sample or the presence of cranial nerve palsy) was present. The 5-year event-free survival and overall survival rates ± SE were 84.2% ± 3.0% and 90.6% ± 2.4%, respectively. No isolated CNS relapse occurred, but two patients experienced combined CNS relapses. The 7-year cumulative risk of any CNS relapse was 1.4% ± 1.0%. Delaying first TIT until circulating blasts have cleared may improve CNS control in children with newly diagnosed ALL and preclude the need for CrRT.Journal of Clinical Oncology 05/2014; 32(17). DOI:10.1200/JCO.2013.54.5020 · 17.88 Impact Factor